Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases

May 2021 Council

Lead Division/Office

DEM, DDN

Point(s) of Contact

Norann Zaghloul, Ph.D.; Maren Laughlin, Ph.D.

Executive Summary

Islet dysfunction is a hallmark of both type 1 and type 2 diabetes. Because of this, decades of study have produced an extensive understanding of islet biology, the vast majority focusing on beta-cells specifically or on islets as independent units distinct from the exocrine pancreas in which they are embedded. The two compartments of the pancreas have traditionally been viewed as discrete non-interacting tissues, despite their shared contribution to regulation of postprandial nutrient absorption. This has resulted in a divide in the study of the pancreas between regulation of digestion (exocrine) and hormonal regulation of metabolism (endocrine) with little overlap between the two. Compelling evidence, however, has challenged this separation and supports the possibility of a greater interaction than previously appreciated. These observations suggest that achieving a more complete understanding of the pancreas as a whole will significantly advance understanding of diseases of both compartments. To target this need, this initiative proposes to solicit applications aimed specifically at characterizing interactions between exocrine and endocrine pancreas. The goal of these projects will be to: 1) elucidate the nature of cross-compartment interactions within the pancreas, 2) understand coordinated regulation of exocrine and endocrine tissues/cells, and 3) define mechanisms by which exocrine-derived cells and/or signaling molecules can contribute to islet function and vice versa.